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Cancer Cell death Cell cycle Cytoskeleton Exo/endocytosis Differentiation Division Organelles Signalling Stem cells Trafficking
Cell Biology International (2009) 33, 882–886 (Printed in Great Britain)
Sub-mitogenic phorbol myristate acetate co-stimulation rescues the PHA-induced activation of both naïve and memory T cells cultured in the rotating-wall vessel bioreactor
Donald M. Simonsa1, Elizabeth M. Gardnerb2 and Peter I. Lelkesa*
aSchool of Biomedical Engineering, Science and Health Systems, Drexel University, 3141 Chestnut St., Bossone Bldg. Rm. 707, Philadelphia, PA 19104, USA
bDepartment of Bioscience and Biotechnology, Drexel University, Philadelphia, PA, USA


Abstract

T lymphocytes are unresponsive to T cell receptor (TCR) stimulation during culture in spaceflight or ground-based microgravity analogs such as the rotating-wall vessel (RWV) bioreactor. The TCR-induced activation of a subset of T cells can be rescued in the RWV by co-stimulation with sub-mitogenic doses of phorbol ester (PMA). We report that PMA co-stimulation of primary human T cells cultured in the RWV rescues the phytohemagglutinin (PHA)-induced activation of the CD8+ and CD4+ T cell subsets as well as naïve and memory CD4+ T cells. Importantly, T cells activated in the RWV by PHA+PMA contained these subsets in proportions strikingly similar to control cultures activated with PHA alone. The data indicate that rescuing T cell activation with PMA co-stimulation does not significantly perturb the heterogeneity of the responding cells, and represent an important proof of principle for the design of immune-boosting agents for use in spaceflight.


Key words: Microgravity, Modeled microgravity, Immune response, Countermeasure.

1Present address: The Wistar Institute, Philadelphia, PA, USA.

2Present address: Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, USA.

*Corresponding author. Tel.: +1215 762 2071; fax: +1215 895 4983.


Received 16 November 2008; accepted 29 April 2009

doi:10.1016/j.cellbi.2009.04.024


ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)